运动神经元病的诊疗现状
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摘要
回顾分析61例我院诊断为运动神经元病患者病例资料,跟踪随访,深入了解其就诊及治疗情况,寻找提高其生存质量及延长生存时间的方法,进一步加深临床医生对运动神经元病患者的认识及关注。对61例就诊于我院诊断为运动神经元病患者的病例资料进行回顾性分析,分别统计其发病年龄,起病形式,确诊时间,影像学资料、治疗方法及其随访资料进行分析。61诊断为运动神经元病的患者,男:女为34:27,平均发病年龄47岁。临床表现多以肢体无力起病,部分患者首发症状为球麻痹。多数患者行肌肉活检及肌电图检查提示神经源性肌肉萎缩。随访患者19例,随访率30.6%。随访19例患者中5例死亡;4例已经卧床,生活不能自理;平均出现时间为在起病后28.3±6.3月;10例表示未见到明显进展。MND起病隐匿,首发症状多样,现阶段的诊断主要依靠临床表现并结合神经电生理及肌肉病理学依据,对该病的治疗尚没有特异性手段,患者治疗并不积极。病程情况因人而异,出现球麻痹后进展较快,生存质量严重受损,生存时间明显下降。临床医生应提高认识,更多关注。
Objective: Retrospective analysis of 61 cases diagnosed in the first hospital of Jilin university in patients as motor neuron disease and follow-up to find out the situation of current diagnosis and treatment of MNDs, and look for the ways improved the quality of life and prolong the living time. To deepen the Clinician awareness of patients and concerns.
Materials and Methods: The data of 61 cases from January 2000 to March 2009 in the First Hospital of Jilin University which all diagnosis as MNDs . Statistics of its prevalence were age, onset forms, diagnosis time, imaging, treatment and follow-up analysis of descriptive information.
Results: In the 61 cases, 34 cases are male,27 cases are female.The average age of onset is 47.8±17.5 years old. The first symptom to diagnosis interval on an average of 27.5±35.5 months.Most patients began with the symptom of limbs weakness,and some of them began with the bulbar paralysis.35 cases of them already have bulbar paralysis.30 cases do the musle biopsy,all of them show the performance of neurogenic muscle atrophy that consistent with motor neuron disease of muscle pathology.53 patients do the EMG, and 48(91 %)cases show the positive neurogenic injury, 4(8%)have a uncertainty result, and one patient's EMG shows diffent results in different hospitals. 19 cases of patients have imaging reports, 7(37%) cases shows cerebral ischemia, 11(58%)have bulging disc, 1(5%) is normal. Follow-up 19 (31.1%) patients after they leaving the hospital. 5(23.8%)cases took the treatment of Riluzole and 2 of them hold on the treatment untilnow. But the other three dropped in after a short time. 4(19.1%)cases took the intravenous injection of Edaravone, which the specific cause is unkown. 8 (38.1%) were insisting in take the medicine treatment of vitamin E. 3 (14.3%) cases have received the treatment of stem cell transplantation. 14(66.7%) cases are under the Chinese medicine treatment. 14 (66.7%) patients have the Difficulty of swallowing,only one of them take the gastrostomy tube feeding. Breathing difficulties are known to occur in 7 (33.3%) cases. Only 1 (14.3%) cases of them take the TIPPV, maintaining 3 months and died because of pulmonary infection and electrolyte disturbance. In the other 6 cases ,3 of them are already died of respiratory failure, the average survival time was 12.3±7.9 months. 2 (9.5%) patients do the training under the professional guidance of doctors. They claimed that musles are more powerful,and the quality of life improved.5 cases died in the 19 patients follow-up of which 4 are died of the respiratory failure. 4 of the 19 cases follow-up are already in bed with out the ability of self-care for an average time of 28.3±6.3 after the onset appears. 10 cases did not see the significant progress that need the long term follow-up.
Conclusion: Motor neron disease is difficulty in diagnosis because of its occult onset. And the diagnosis of it often based on the symptomatic features of the patients and need the supports of the EMG and musle biopsy reports. There is no specific treatment method,the ways to treat always be the symptomatic and supportive treatment. The progression of MND depends on the individual. It goes fast when the bulbar paralysis happened. The survival time and the quality of life declined rapidly. We should pay more attention to the patients with MNDs and do better follow-up and management.
Objective: Retrospective analysis of 61 cases diagnosed in the first hospital of Jilin university in patients as motor neuron disease and follow-up to find out the situation of current diagnosis and treatment of MNDs, and look for the ways improved the quality of life and prolong the living time. To deepen the Clinician awareness of patients and concerns.
Materials and Methods: The data of 61 cases from January 2000 to March 2009 in the First Hospital of Jilin University which all diagnosis as MNDs . Statistics of its prevalence were age, onset forms, diagnosis time, imaging, treatment and follow-up analysis of descriptive information.
Results: In the 61 cases, 34 cases are male,27 cases are female.The average age of onset is 47.8±17.5 years old. The first symptom to diagnosis interval on an average of 27.5±35.5 months.Most patients began with the symptom of limbs weakness,and some of them began with the bulbar paralysis.35 cases of them already have bulbar paralysis.30 cases do the musle biopsy,all of them show the performance of neurogenic muscle atrophy that consistent with motor neuron disease of muscle pathology.53 patients do the EMG, and 48(91 %)cases show the positive neurogenic injury, 4(8%)have a uncertainty result, and one patient's EMG shows diffent results in different hospitals. 19 cases of patients have imaging reports, 7(37%) cases shows cerebral ischemia, 11(58%)have bulging disc, 1(5%) is normal. Follow-up 19 (31.1%) patients after they leaving the hospital. 5(23.8%)cases took the treatment of Riluzole and 2 of them hold on the treatment untilnow. But the other three dropped in after a short time. 4(19.1%)cases took the intravenous injection of Edaravone, which the specific cause is unkown. 8 (38.1%) were insisting in take the medicine treatment of vitamin E. 3 (14.3%) cases have received the treatment of stem cell transplantation. 14(66.7%) cases are under the Chinese medicine treatment. 14 (66.7%) patients have the Difficulty of swallowing,only one of them take the gastrostomy tube feeding. Breathing difficulties are known to occur in 7 (33.3%) cases. Only 1 (14.3%) cases of them take the TIPPV, maintaining 3 months and died because of pulmonary infection and electrolyte disturbance. In the other 6 cases ,3 of them are already died of respiratory failure, the average survival time was 12.3±7.9 months. 2 (9.5%) patients do the training under the professional guidance of doctors. They claimed that musles are more powerful,and the quality of life improved.5 cases died in the 19 patients follow-up of which 4 are died of the respiratory failure. 4 of the 19 cases follow-up are already in bed with out the ability of self-care for an average time of 28.3±6.3 after the onset appears. 10 cases did not see the significant progress that need the long term follow-up.
Conclusion: Motor neron disease is difficulty in diagnosis because of its occult onset. And the diagnosis of it often based on the symptomatic features of the patients and need the supports of the EMG and musle biopsy reports. There is no specific treatment method,the ways to treat always be the symptomatic and supportive treatment. The progression of MND depends on the individual. It goes fast when the bulbar paralysis happened. The survival time and the quality of life declined rapidly. We should pay more attention to the patients with MNDs and do better follow-up and management.
引文
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[16]Nagata T,Nagano I,Shiote M,et al.Elevation of MCP-1 and MCP-1/VEGF ratio in cerebr ospinal fluid of amyotrophic lateral sclerosis patients[J].Neurol Res,2007,29(8):772-776.
[17]Osthuyse B,Moons L,Storkebaum E,et al.Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration[J].Nat Genet,2001,28:131-138.
[18]Scheufler KM,Drevs J,van Velthoven V,et al.Implications of vascular endothelial growth factor:sFlt-1,and sTie-2 in plasma,serum and cerebrospinal fluid during cerebral ischemia in man[J].J Cereb Blood Flow Metab,2003,23:99-110.
[19]Nygren I,Larsson A,Johansson A,et al.VEGF is increased in serum but not in spinal cord from patients with amyotrophic lateral sclerosis[J].NeuroReport,2002,13:2199-2201.
[20]Matsuzaki H,Tamatani M,Yamaguchi A,et al.Vascular endothelial growth factor rescues hippocampal neurons from glutamate-induced toxicity:signal transduction cascades[J].FASEB J,2001,15:1218-2120.
[21]郝洪军,杨纳莲,任士卿,等.肌萎缩侧索硬化患者脑脊液免疫指标检测的意义[J].中国临床康复,2005,9(25):24-27.
[22]Ito H,Wate R,Zhang J,et al.Treatment with edaravone,initiated at symptom onset,slows motor decline and decreases SOD1 deposition in ALS mice[J].Eur J Neurol,2008,213(2):448-55.
[23]Dalbello Has V,Florence JM,Krivickas LS.Therapeutic exercise for people with amyotrophic lateral sclerosis or motor neuron disease[J].Cochrane Database Syst Rev,2008,16(2):5229.
[24]Rosenfeld J,Ellis A.Nutrition and dietary supplements in motor neuron disease[J].Phys Med Rehabil Clin N Am,2008,19(3):573-589.
[25]Czaplinski A,Schweikert K,Strobel W,et al.Symptomatic manage- ment in amyotrophic lateral sclerosis(ALS) Praxis[J].Eur J Neurol,2006,95(8):263-8,269-71.
[26]Vignola A,Guzzo A,Calvo A,et al.Anxiety undermines quality of life in ALS patients and caregivers[J].Eur J Neurol,2008,15(11):1231-6.
[27]Gil J,Funalot B,Verschueren A,et al.Causes of death amongst French patients with amyotrophic lateral sclerosis:a prospective study[J].Eur J Neurol.2008,15(11):1245-51.
[28]崔丽英,樊东升,运动神经元病协作组,2008年第11届全国神经病学学术会.
[29]Verschueren A,Monnier A,Attarian S,et al.Enteral and parenteral nutrition in the later stages of ALS:an observational study[J].Amyotroph Lateral Scler,2009,2,10(1):42-46.
[30]Simmons Z.Management strategies for patients with amyotrophic lateral sclerosis from diagnosis through death[J].Neurologist,2005,11(5):257-270.
[31]Deda H,Inci M,Kurekci A,et al.Treatment of amyotrophic lateral sclerosis patients by autologous bone marrow-derived hematopoietic stem cell transplantation:a 1-year follow-up[J].Cytotherapy,2008,11,15:1-8.
[32]樊东升.第17届世界神经病学大会肌萎缩侧索硬化专题纪要[J].中华神经科杂志,2002,35(2):122-123.
[33]Brooks BR.Managing amyotrophic lateral sclerosis:slowing disease progression and improving patient quality of life[J].Ann Neurol,2009,1,65(1):17-23.
[34]Atsuta N,Watanabe H,Ito M.Age at onset influences on wide-ranged clinical features of sporadic amyotrophic lateral sclerosis[J].J Neurol Sci,2009,1,276(1-2):163-9.
[35]Danel-Brunaud V,Laurier L,Parent K.Issues of France's "Leonetti Act":Involvement of amyotrophic lateral sclerosis patients in prior discussions concerning respiratory support and end-of-life care[J].Rev Neurol(Paris),2009,2,165(2):170-177.
[36]高飞,樊东升,张燕.运动神经元病患者睡眠及心境情况调查,第2届中国睡眠医学论坛论文汇编,2007,131-132.
[37]Fang F,Valdimarsdrttir U,Furst CJ.Suicide among patients with amyotrophic lateral sclerosis[J].Brain,2008,131(10):2729-2733.
[38]Uetake H.What must we do for patients with ALS in the process of their decision making on TIPPV?[J].Rinsho Shinkeigaku,2008;11,48(11):961-962.
[2]Saltiel AR,Pessin JE.Insulin signaling Pathways in time and space [J].Trends Cell Biol,2002,12:65-71.
[3]Kurtzke JF.Risk factors in amyotrophic lateral sclerosis:Amyotrophic lateral sclerosis and other motor neuron disease [M].New York Raven Press,2001,2:45.
[4]Rothstein JD,Martin J,Kunel RW.Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis [J].N Engl J Med,1992,236:1464.
[5]Tsan G,Gord LC,Slusber BS,et al.Abnormal acidic amino acids and N-acety lasparty lglutamate in Hereditary canine motrneuron disease [J].Brain Res,1993,629:305.
[6]Volterra A,Trotti D,Trnmba C,et al.Glutamate uptake inhibition by oxygeu free radicals in rat cortical astrocytes [J].J Neurosci,1994,14(5):292.
[7]Duarte L,Binet S,Lacomblez L,et al.Quaniftative analysis of monoclonal immunoglobulins in Serum of patients with amyotrophic taieral sclerosis[J].J Neurol ScL,1991,194(1):8.
[8]Engelhardt JI,Appel SH,Kiilian JM.Motorneuron destruction on guinea pigs immunized with bovine spinal cord ventral hom homogenate:experimental autoimmune gray matter diseas[J].J Neuroimmunal,1990,27:21.
[9]Kimura F,Smith RG,Delbono O,et al.Amyotrophie lateral sclerosis patient antibodies label Ca2+ channel alpha 1 subunit[J].Ann Neurol,1994,35(2):164.
[10]Woolley SC,Jonathan S Katz.Cognitive and behavioral impairment in amyotrophic lateral sclerosis[J].Phys Med Rehabil Clin N Am,2008,19(3):607-17.
[11]宋小燕.肌萎缩侧索硬化的自主神经功能障碍[J].Jounal of International Neurlogy and Neurosurgery,2007,34(3):274-277.
[12]Brooks BR,Miller R G,Swash M,et al.E1 Escorial revisited:Revised criteria for the diagnosis of amyotrophic lateral sclerosis[J].ALS and other motom euron diorders,2000,1:293-299.
[13]中华医学会神经病学分会.肌萎缩侧索硬化的诊断标准(草案)[J].中国神经科杂志,2001,34(3):190.
[14]樊东升.关注肌萎缩侧索硬化患者的临床诊治[J].中国现代神经疾病杂志,2005,5(5),287-288.
[15]徐艳炜,谢炳玓,翟翚,等.弥散张量成像对早期肌萎缩侧索硬化症上运动神经元损害的诊断意义[J].天津医药,2009,37(1),31-33.
[16]Nagata T,Nagano I,Shiote M,et al.Elevation of MCP-1 and MCP-1/VEGF ratio in cerebr ospinal fluid of amyotrophic lateral sclerosis patients[J].Neurol Res,2007,29(8):772-776.
[17]Osthuyse B,Moons L,Storkebaum E,et al.Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration[J].Nat Genet,2001,28:131-138.
[18]Scheufler KM,Drevs J,van Velthoven V,et al.Implications of vascular endothelial growth factor:sFlt-1,and sTie-2 in plasma,serum and cerebrospinal fluid during cerebral ischemia in man[J].J Cereb Blood Flow Metab,2003,23:99-110.
[19]Nygren I,Larsson A,Johansson A,et al.VEGF is increased in serum but not in spinal cord from patients with amyotrophic lateral sclerosis[J].NeuroReport,2002,13:2199-2201.
[20]Matsuzaki H,Tamatani M,Yamaguchi A,et al.Vascular endothelial growth factor rescues hippocampal neurons from glutamate-induced toxicity:signal transduction cascades[J].FASEB J,2001,15:1218-2120.
[21]郝洪军,杨纳莲,任士卿,等.肌萎缩侧索硬化患者脑脊液免疫指标检测的意义[J].中国临床康复,2005,9(25):24-27.
[22]Ito H,Wate R,Zhang J,et al.Treatment with edaravone,initiated at symptom onset,slows motor decline and decreases SOD1 deposition in ALS mice[J].Eur J Neurol,2008,213(2):448-55.
[23]Dalbello Has V,Florence JM,Krivickas LS.Therapeutic exercise for people with amyotrophic lateral sclerosis or motor neuron disease[J].Cochrane Database Syst Rev,2008,16(2):5229.
[24]Rosenfeld J,Ellis A.Nutrition and dietary supplements in motor neuron disease[J].Phys Med Rehabil Clin N Am,2008,19(3):573-589.
[25]Czaplinski A,Schweikert K,Strobel W,et al.Symptomatic manage- ment in amyotrophic lateral sclerosis(ALS) Praxis[J].Eur J Neurol,2006,95(8):263-8,269-71.
[26]Vignola A,Guzzo A,Calvo A,et al.Anxiety undermines quality of life in ALS patients and caregivers[J].Eur J Neurol,2008,15(11):1231-6.
[27]Gil J,Funalot B,Verschueren A,et al.Causes of death amongst French patients with amyotrophic lateral sclerosis:a prospective study[J].Eur J Neurol.2008,15(11):1245-51.
[28]崔丽英,樊东升,运动神经元病协作组,2008年第11届全国神经病学学术会.
[29]Verschueren A,Monnier A,Attarian S,et al.Enteral and parenteral nutrition in the later stages of ALS:an observational study[J].Amyotroph Lateral Scler,2009,2,10(1):42-46.
[30]Simmons Z.Management strategies for patients with amyotrophic lateral sclerosis from diagnosis through death[J].Neurologist,2005,11(5):257-270.
[31]Deda H,Inci M,Kurekci A,et al.Treatment of amyotrophic lateral sclerosis patients by autologous bone marrow-derived hematopoietic stem cell transplantation:a 1-year follow-up[J].Cytotherapy,2008,11,15:1-8.
[32]樊东升.第17届世界神经病学大会肌萎缩侧索硬化专题纪要[J].中华神经科杂志,2002,35(2):122-123.
[33]Brooks BR.Managing amyotrophic lateral sclerosis:slowing disease progression and improving patient quality of life[J].Ann Neurol,2009,1,65(1):17-23.
[34]Atsuta N,Watanabe H,Ito M.Age at onset influences on wide-ranged clinical features of sporadic amyotrophic lateral sclerosis[J].J Neurol Sci,2009,1,276(1-2):163-9.
[35]Danel-Brunaud V,Laurier L,Parent K.Issues of France's "Leonetti Act":Involvement of amyotrophic lateral sclerosis patients in prior discussions concerning respiratory support and end-of-life care[J].Rev Neurol(Paris),2009,2,165(2):170-177.
[36]高飞,樊东升,张燕.运动神经元病患者睡眠及心境情况调查,第2届中国睡眠医学论坛论文汇编,2007,131-132.
[37]Fang F,Valdimarsdrttir U,Furst CJ.Suicide among patients with amyotrophic lateral sclerosis[J].Brain,2008,131(10):2729-2733.
[38]Uetake H.What must we do for patients with ALS in the process of their decision making on TIPPV?[J].Rinsho Shinkeigaku,2008;11,48(11):961-962.